摘要:

Background In autopsy, myocardial bridging is a common finding. With coronary angiography, a systolic compression, mainly of the left anterior descending coronary artery, is observed in 1% to 3% of the patients. Controversy exists concerning the functional importance of this finding. To obtain a functional insight into the myocardial bridging, intravascular ultrasound and intracoronary Doppler were performed.Methods and Results Intracoronary ultrasound and Doppler were performed in 14 patients with angiographic evidence of systolic vessel compression ("milking effect") in the left anterior descending coronary artery. The 4.8F, 20-MHz ultrasound catheter could not be advanced through the entire myocardial bridge segment in 6 of the 14 patients studied because the lumen was <1.6 mm. In these patients, only the proximal parts of the bridge segment were scanned. The changes in cross-sectional shape during the cardiac cycle were determined for both the normal proximal segment and the bridge segment by use of a semiautomatic computer program. Intracoronary Doppler (20 MHz) was performed in 7 patients with a 3F catheter. A highly characteristic systolic eccentric or concentric compression with delayed relaxation in diastole of the myocardial bridging segment was clearly visualized in all patients. The cross-sectional lumen area variation was 40+-25% in the bridging segments and 9+-7% in the normal segments (P<.01). No atherosclerotic lesions were detected in the bridge or the distal segment in the 8 patients in whom the IVUS catheter was successfully advanced through the entire myocardial bridge. However, atherosclerotic plaques were found in the segments proximal to the bridge in 12 of 14 patients (86%). The resting mean flow velocity was 6.4+-1.2 cm/s; the maximal mean flow velocity after intracoronary administration of 10 mg papaverine was 14.1+-3.4 cm/s. The coronary flow velocity reserve was 2.2+-0.7. A highly characteristic pattern showing a prominent peak in coronary velocity in early diastole was observed in 86% of patients, and this pattern was enhanced after injection of intracoronary papaverine.Conclusions Intravascular ultrasound demonstrated a characteristic systolic compression of the bridge segments. The delayed compression release may explain the characteristic sharp early diastolic peak in coronary flow velocity found with intracoronary Doppler in vessels with myocardial bridging. Reduced coronary flow reserve may be related to this phenomenon, possibly explaining signs of ischemia detected in some of the patients, but may alternatively be a result of the presence of atherosclerosis in the segment proximal to the bridge in these patients. (Circulation. 1994;89:1725-1732.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The prognosis of patients with primary pulmonary hypertension (PPH) remains a major problem for the planning and assessment of therapeutic interventions. The objectives of this study were (1) to characterize mortality in a Mexican population of patients with PPH and to investigate factors associated with survival and (2) to test the applicability in this population of the prognostic equation proposed by the US National Institutes of Health study on PPH.Methods and Results A dynamic cohort of patients with PPH at our institution were enrolled between June 1977 and August 1991 and prospectively followed at regular intervals through September 1992. Measurements at diagnosis included hemodynamic and pulmonary function variables in addition to information on demographic data and medical history. The response to vasodilator treatment was also analyzed. The estimated median survival of the group was 4.04 years (95% confidence interval, 2.98 to 5.08 years). Variables associated with poor survival (univariate analysis) included an elevated mean right atrial pressure, a decreased cardiac index, and a decreased mixed venous Po2. A reduced forced vital capacity and the absence of vasodilator treatment were also associated with poor survival. A multivariate Cox proportional-hazards regression analysis was used to assess the adjusted hazard ratios, hence the relative contributions of the variables controlling for confounding. Reduced forced vital capacity and cardiac index and increased right atrial pressure were still significantly associated as risk factors for survival in patients with PPH. Survival as computed by the equation correlated with real survival of PPH patients with positive predictive values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation, however, was relatively unable to predict deaths in our population, in part because of the strict limits of poor prognosis.Conclusions Mortality in PPH is largely associated with hemodynamic variables that assess right ventricular function. The proposed prognostic equation had a high sensitivity and a relatively low specificity to predict survival in our PPH population. To improve this specificity it may be necessary to increase the limits of poor prognosis as defined by the equation. (Circulation. 1994;89:1733-1744.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Despite successful repair of coarctation of the aorta in childhood, adult survivors often have hypertension at rest or on exercise, and their life expectancy is shorter than normal because of premature coronary and cerebrovascular disease. This may be related to persistent structural and functional arterial abnormalities after surgery.Methods and Results Using high-resolution ultrasound, we studied the right brachial arteries of 25 normotensive young adults who had undergone successful repair of coarctation in childhood (mean age at repair, 62 months; range, 0 to 167 months, including 8 patients operated on in infancy; mean age at study, 19 years; range, 14 to 27 years) and 50 age- and sex-matched control subjects. We assessed the degree of reactive hyperemia (RH) produced after distal cuff occlusion and release and the changes in arterial diameter in response to RH (with increased flow causing endothelium-dependent dilation) and to glyceryltrinitrate (GTN, an endothelium-independent dilator). The response of the right femoral artery to GTN was also measured in 12 coarctation subjects and 12 control subjects. Studies were performed 13.7 years (range, 7 to 21 years) after surgery. RH was significantly lower in coarctation subjects (343+-130% versus 482+-147%), as were endothelium-dependent dilation (3.8+-3.3% versus 8.8+-3.6%) and GTN response (13.3+-6.0% versus 20.5+-6.1%) (P<.001 for each), reflecting abnormal dilatory capacity in both the resistance and conduit arteries. In contrast, GTN-induced dilation in the femoral arteries was similar to that in control subjects (9.5+-2.6% versus 10.1+-4.1%, P=.70). On multivariate analysis, GTN response and systolic blood pressure at peak exercise were inversely correlated (r=-.52, P=.04). Vascular responses were not related to the age at repair.Conclusions Despite successful repair of coarctation in childhood, arterial dilation is significantly impaired in the precoarctation vascular bed of healthy young adults. This may be an important contributor to exercise-related hypertension and late morbidity or mortality. (Circulation. 1994;89: 1745-1750.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background This study was performed to determine independent predictors of long-term outcome after percutaneous balloon dilation of congenital pulmonary valve stenosis. Smaller follow-up series of patients after balloon pulmonary valvuloplasty have shown inconsistent results regarding the independent relation between prognostic factors and long- term outcome, as many patient selection and technical factors are correlated.=36 mm Hg or further treatment of pulmonary stenosis requiring repeat balloon pulmonary valvuloplasty or surgical therapy. Significant independent predictors of a suboptimal long-term outcome included an earlier study year of the initial valvuloplasty (adjusted odds ratio, 0.71 per consecutive year), a small valve hinge point diameter (0.81 per 1-mm increase), and a higher immediate residual gradient (1.32 per 10 mm Hg increase). A smaller ratio of balloon to valve hinge point diameter significantly predicted suboptimal outcomes for patients with valve morphologies classified as typical (0.52 per 0.1 increase in ratio) and complex (primarily postsurgical valvotomy, 0.43) but not for patients with dysplastic (0.95) or combined morphologies (dysplasia with commissural fusion, 1.01). Patient age, the presence of Noonan's syndrome or associated cardiac lesions, pre-balloon valvuloplasty hemodynamic parameters, and the use of a simulta neous double-balloon technique did not independently predict follow-up outcomes.Conclusions Accurate prognostication after balloon pulmonary valvuloplasty depends on the careful determination of valvar anatomy. The use of an appropriate ratio of balloon to valve hinge point diameter in the setting of typical valve morphology will optimize the chance of long-term success. (Circulation. 1994;89:1751-1759.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Cell adhesion molecules (CAMs) have been implicated in cardiac allograft rejection. However, previous studies have used qualitative analysis of immunohistochemical data and did not exclude patients with infection or malignancy.Methods and Results We analyzed 40 endomyocardial biopsy specimens from 25 cardiac transplant patients and 8 specimens from patients undergoing cardiac surgery. Patients with evidence of infection or malignancy were excluded. Specimens were stained with monoclonal antibodies against ICAM-1, E-selectin, VCAM-1, and PECAM-1 (which labels all vessels). ICAM-1 expression was assessed by counting ICAM-1-positive vessels and dividing by the total number of vessels (measured by PECAM staining). Specimens were scored as positive or negative for VCAM-1 and E-selectin. We also determined whether serum-soluble ICAM-1 levels (sICAM) correlated with rejection by evaluating 145 serum specimens from 48 cardiac transplant patients and 8 specimens from patients undergoing diagnostic cardiac catheterization. ICAM-1 was present on 50% to 60% of vessels in normal and nonrejecting specimens. Specimens with histologically significant rejection (focal moderate, moderate, or severe) had an increased percentage of ICAM-1-positive vessels: focal moderate, 77%; moderate/severe, 92% (P<.01). E-selectin expression did not differ between groups. VCAM-1 frequently was not present on rejecting specimens. No correlation was noted between sICAM levels and the presence or absence of rejection.Conclusions (1) ICAM-1 expression is strongly correlated with histologically significant cardiac allograft rejection. (2) The use of PECAM-1 staining as a vascular marker permits quantitative analysis of ICAM-1 expression. (3) VCAM-1 and E-selectin are not consistently increased during cardiac allograft rejection. (4) sICAM levels do not accurately reflect endomyocardial biopsy results. (Circulation. 1994;89:1760-1768.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background The major purpose of the present study was to determine the effect of the potassium channel opener bimakalim, administered intracoronary only during the initial 10 minutes of ischemia, on myocardial infarct size in anesthetized dogs. A second aim was to test the possibility that bimakalim mediates its cardioprotective effects by accelerating the rate of myocyte action potential shortening during early ischemia. A third aim was to determine the relative potency of bimakalim to open coronary vascular ATP-regulated potassium (KATP) channels versus myocyte KATPchannels.Methods and Results Barbital-anesthetized open-chest dogs were used. In the initial studies, bimakalim (0.1 to 10 micrograms/min) was infused into the left anterior descending coronary artery (LAD), and changes in coronary blood flow and monophasic action potential duration (MAPD) were used as indexes of coronary vascular KATPchannel and myocyte KATPchannel activity, respectively. In subsequent infarct studies, dogs were subjected to 60 minutes of LAD occlusion followed by 4 hours of reperfusion. Based on preliminary studies, two doses of bimakalim that did not shorten MAPD during nonischemic conditions (0.1 and 0.3 micrograms/min) and one that markedly shortened MAPD during nonischemic conditions (3.0 micrograms/min) or an equal volume of vehicle were infused into the LAD during the initial 10 minutes of coronary artery occlusion. Transmural myocardial blood flow was measured at 5 and 30 minutes of occlusion by the radioactive microsphere technique, and infarct size was determined at the end of 4 hours of reperfusion by triphenyltetrazolium staining. The monophasic action potential duration at 50% repolarization (MAPD50) was measured by an epicardial probe placed in the center of the ischemic area. Bimakalim had an approximately 10-fold greater affinity for the coronary vascular than the myocardial KATPchannel (ED50coronary, (approximately) 0.3 micrograms/min; ED50myocyte, (approximately) 3.0 micrograms/min). Three doses of bimakalim (0.1, 0.3, and 3.0 micrograms/min) all markedly reduced infarct size expressed as percent of the area at risk (12.6+-3.3%, 14.5+-2.2%, and 14.2+-5.3%, respectively, versus 27.2+-5.7% in controls) to nearly equal extents. Subsequently, we found that the two higher doses of bimakalim (0.3 and 3.0 micrograms/min) markedly accelerated yet the 0.1-micrograms/min dose of bimakalim did not significantly affect the ischemia-related shortening of the action potential during the initial 5 minutes of occlusion. In addition, 0.1 and 0.3 micrograms/min bimakalim did not increase the incidence of ventricular fibrillation during the 60 minutes of occlusion (0 of 7 and 0 of 8 dogs, respectively), whereas 3.0 micrograms/min bimakalim had a profibrillatory effect (6 of 6) compared with the control group (1 of 8). There were no significant differences between groups in systemic hemodynamics, myocardial oxygen demand, ischemic bed size, or collateral blood flow to the ischemic region.Conclusions The results of the present study clearly reveal that a small dose (0.1 or 0.3 micrograms/min) of the KATPchannel opener bimakalim administered only during the initial 10-minute period of ischemia markedly reduced myocardial infarct size to an extent equal to that of a higher profibrillatory dose in barbital-anesthetized dogs. These data also suggest that bimakalim and other potassium channel openers may partially exert their cardioprotective effects by accelerating KATPchannel activation during early ischemia as evidenced by an enhanced rate of ischemic myocyte action potential shortening. However, the results also suggest that other cellular mechanisms may be involved in mediating the cardioprotection produced by a low dose of bimakalim (0.1 micrograms/min) because it did not significantly accelerate the shortening of the action potential duration, yet it had an efficacy to reduce myocardial infarct size similar to that of the two higher doses. (Circulation. 1994;89:1769-1775.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Endothelium-dependent, pertussis toxin-sensitive relaxation to 5-hydroxytryptamine (5-HT) is impaired selectively after balloon injury of porcine coronary artery, followed by regeneration of the endothelial cells. The present study was designed to test the hypothesis that 5-HT, released from aggregating platelets, affects the progression of the endothelial dysfunction.Methods and Results Yorkshire pigs were assigned randomly to three groups: control group (standard diet), denudation group (high-cholesterol diet plus balloon denudation of the endothelium of coronary artery under fluoroscopy), and DV-7028-treated group (denudation group plus chronic treatment with the selective 5-HT2receptor antagonist DV-7028, given from the first day on after balloon denudation). Four weeks after the denudation, quantitative angiography revealed that 5-HT injected into the coronary artery decreased the luminal diameter of the left anterior descending coronary artery at the denuded site in the denudation group but not in the control or the DV-7028-treated group. Then, animals were killed so we could study the endothelium-dependent responses of their coronary arteries in conventional organ chambers. The arteries from the denudation group exhibited less relaxation to 5-HT and sodium fluoride (a stimulant of G proteins) than those of the control group. Relaxations to 5-HT and sodium fluoride were greater in arteries from the DV-7028-treated group than in those from the denudation group. In contrast, the endothelium-dependent, pertussis toxin-insensitive relaxations to bradykinin and thrombin and the endothelium-independent relaxations to sodium nitroprusside and isoproterenol were not affected significantly by chronic treatment with DV-7028.Conclusions These results suggest that 5-HT2receptors are involved in the chronic progression of endothelial dysfunction after balloon denudation in the porcine coronary artery. (Circulation. 1994;89:1776-1785.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background Prostaglandin E sub 1 is a potent vasodilator with anti-inflammatory and antiplatelet effects. We tested the hypothesis that prostaglandin E1attenuates or prevents platelet aggregation-associated cyclic flow variations (CFVs) in severely stenosed and endothelium-injured coronary arteries.Methods and Results We induced CFVs in 21 dogs by placing an external constrictor around the left anterior descending coronary artery at the site where the endothelium had been mechanically injured. The blood flow velocity in the artery was monitored by a pulsed Doppler flow probe. Sixty minutes after CFVs were established, liposome-bound prostaglandin E1, a stable formulation, was administered intravenously to 12 dogs at incremental doses of 0.25, 0.5, 1, and 2 micrograms/kg body wt; it abolished CFVs in 8 of the 12 dogs (67%). After CFVs were eliminated, epinephrine was infused intravenously, and at a dose of 6.6+-1.6 micrograms/min, it restored CFVs in 7 of 7 dogs. Control dogs (n=9) were treated with free prostaglandin E1, which did not abolish CFVs in any dog.Conclusions Liposome-bound but not free prostaglandin E1effectively diminishes CFVs in severely stenosed and endothelium-injured canine coronary arteries. (Circulation. 1994; 89:1786-1791.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background There has been controversy about whether early reperfusion of myocardial infarcts causes further necrosis mediated by reactive oxygen species or other mechanisms. Unequivocal evidence that therapeutic agents given only during reperfusion can prevent, rather than delay or modify, injury has been sparse. Failure to account for variables, such as collateral blood flow, that influence infarct size independently and attempts to measure infarct size too early in reperfusion may have limited the sensitivity and specificity of some previous studies.Methods and Results After 90 minutes of coronary occlusion and 48 hours of reperfusion in a canine model, we examined the effect on infarct size of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible antioxidant. Infarct size and region at risk were measured by postmortem dual perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional myocardial blood flow was measured with radioactive microspheres. Infusion of MPG 100 mg x kg sup -1 x h sup -1, beginning either 15 minutes before the onset of reperfusion or 30 minutes after the onset of reperfusion and continued until 4 hours of reperfusion and followed by an intramuscular dose, reduced infarct size, normalized for both region at risk and the level of collateral blood flow, by 60% and 45%, respectively. When infusion of MPG was limited to the last 15 minutes of ischemia and the first hour of reperfusion only, the normalized infarct size was reduced by 26%. Heart rate, blood pressure, and their product did not differ among the four groups studied. The plasma half-time of MPG was <10 minutes. In in vitro experiments MPG was a scavenger of hydrogen peroxide but not of superoxide radical.Conclusions After 90 minutes of coronary ligation, infusion of the diffusible hydrogen peroxide scavenger, MPG, for several hours, beginning as late as 30 minutes after the onset of reperfusion, substantially reduced infarct size measured 48 hours later. In this model, necrosis caused by processes during reperfusion may be more extensive than necrosis caused by ischemia alone. Since infusion of this agent for only the first hour of reperfusion was considerably less effective, it appears that most of the oxidant injury leading to necrosis occurred after the first 60 minutes but within the first 4 hours of reperfusion. (Circulation. 1994;89:1792-1801.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background We evaluated the effects of a novel platelet fibrinogen receptor antagonist, Integrelin, and a direct thrombin inhibitor, recombinant hirudin, given together with recombinant tissue plasminogen activator (rTPA) in a canine experimental model of intracoronary thrombosis. We tested the hypothesis that combination of both agents at low doses would have an additive antithrombotic effect, resulting in a significant improvement in the efficacy of rTPA.Methods and Results Thirty-two dogs with an electrically induced coronary thrombus were treated with rTPA (1 mg/kg over 20 minutes) together with one of the following adjunctive treatments in a random fashion. Eight dogs received saline for 90 minutes; Integrelin (5 micrograms x kg sup -1 x min sup -1 for 90 minutes) was given to 8 dogs; 8 dogs received recombinant hirudin (20 micrograms x kg sup -1 x min sup -1 for 90 minutes); and 8 dogs were treated with a low-dose combination of Integrelin (2.5 micrograms x kg sup -1 x min sup -1) plus recombinant hirudin (10 micrograms x kg sup -1 x min sup -1) for 90 minutes. Integrelin or recombinant hirudin, when given as single adjunct to rTPA, enhanced the lysis of the occlusive thrombus, causing full restoration of coronary blood flow (100% of its baseline value) for 29+-16 and 26+-5 minutes, respectively, whereas coronary blood flow was fully restored for only 5+-1 minutes in dogs receiving rTPA plus saline (both P<.05). However, either Integrelin or recombinant hirudin failed to modify the reocclusion rate (57% and 63%, respectively) compared with saline (83%; all P=NS). Conversely, the low-dose combination therapy led to complete restoration of coronary blood flow for 92+-19 minutes (P<.01 versus all treatments) and significantly reduced the reocclusion rate (25%; P<.05 versus saline).Conclusions These data show that inhibition of specific pathways of platelet and thrombin activity improves the extent and duration of rTPA-induced thrombolysis in the electrolytic canine model. Furthermore, our findings suggest that low doses of platelet IIb/IIIa and direct thrombin antagonists in combination may be used successfully during thrombolysis. (Circulation. 1994;89:1802-1809.)

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID